6-43582370-TTTTG-T

Position:

• chr6-43582370-TTTTG-T

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_006502.3(POLH):​c.54_57del​(p.Val19LysfsTer10) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: POLH NM_006502.3 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.78

Genes affected

POLH (HGNC:9181): (DNA polymerase eta) This gene encodes a member of the Y family of specialized DNA polymerases. It copies undamaged DNA with a lower fidelity than other DNA-directed polymerases. However, it accurately replicates UV-damaged DNA; when thymine dimers are present, this polymerase inserts the complementary nucleotides in the newly synthesized DNA, thereby bypassing the lesion and suppressing the mutagenic effect of UV-induced DNA damage. This polymerase is thought to be involved in hypermutation during immunoglobulin class switch recombination. Mutations in this gene result in XPV, a variant type of xeroderma pigmentosum. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2014]

POLR1C (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 16 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 6-43582370-TTTTG-T is Pathogenic according to our data. Variant chr6-43582370-TTTTG-T is described in ClinVar as [Pathogenic]. Clinvar id is 5885.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLH	NM_006502.3	c.54_57del	p.Val19LysfsTer10	frameshift_variant	2/11	ENST00000372236.9	NP_006493.1
POLH	NM_001291970.2	c.54_57del	p.Val19LysfsTer10	frameshift_variant	2/11		NP_001278899.1
POLH	NM_001291969.2	c.-17-634_-17-631del		intron_variant			NP_001278898.1
POLR1C	NM_001318876.2	c.945+53102_945+53105del		intron_variant			NP_001305805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLH	ENST00000372236.9	c.54_57del	p.Val19LysfsTer10	frameshift_variant	2/11	1	NM_006502.3	ENSP00000361310	P1
POLH	ENST00000372226.1	c.54_57del	p.Val19LysfsTer10	frameshift_variant	2/11	1		ENSP00000361300
POLH	ENST00000443535.1	c.-49-634_-49-631del		intron_variant		2		ENSP00000405320

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Xeroderma pigmentosum variant type Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 17, 1999

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-43550107;